Nephrotoxicity and highly active antiretroviral therapy: Mitigating action of Momordica charantia.

Ugochukwu Offor,Onyemaechi Okpara Azu,Aniekan Imo Peter,Oluwatosin Olalekan Ogedengbe,Edwin Coleridge Naidu,Ayoola Isaac Jegede

doi:10.1016/j.toxrep.2018.09.003

Abstract

Momordica charantia (M. charantia) is known for its antioxidant and antidiabetic properties. The aim of this study is to investigate the renoprotective effects of M. charantia in rats following treatment with highly active antiretroviral therapy (HAART) regimen triplavar. Adult male Sprague-Dawley rats weighing 178.1-220.5 g (n = 36) were divided into six groups (A-F) with each group comprising of six (n = 6) rats. The drugs and extract were administered via oral gavage. The therapeutic dose of triplavar was adjusted using the human therapeutic dose equivalent for the rat model. Animals were euthanized on the tenth week with kidneys removed for examination and blood obtained via cardiac puncture. Levels of oxidative stress enzymes (superoxide dismutase-SOD, catalase-CAT, and reduced glutathione-GSH) were significantly lowered in all groups not receiving M. charantia. The levels of thiobarbituric acid reactive substances (TBARS) were increased resulting in free radical formation via auto-oxidation. Renal parameters showed no albuminuria, normal blood urea nitrogen (BUN), serum creatinine (SCr) and electrolytes in groups treated with M. charantia. HAART treated (Group B) showed severe albuminuria, a significantly (p < 0.05) raised BUN and SCr and gross electrolyte disturbances. Blood glucose levels were significantly raised in groups not receiving the adjuvant M. charantia (p < 0.05). Histopathology in HAART treated animals showed glomerular capillary abnormalities and cellular infiltrations while M. charantia treated animals showed an essentially normal glomerular appearance with capillary loops and normal cytoarchitecture. In conclusion M. charantia extract administration improved blood glucose levels, restored renal histology, reinstate renal function, reduce body weight loss and restores hyperglycemia.

Highlights

The successful introduction of highly active antiretroviral therapy (HAART) for the management of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) significantly increased the life expectancy among HIV-infected patients with unprecedented changes in disease progression and mortality [1]. Despite this full control, empirical evidence still demonstrates that nephrotoxicity is increasing rapidly among people living with HIV and AIDS (PLWHA) dampening the perceived impact of HAART
While there was an overall increase in body weight (BW) in all groups, Groups, C and E recorded maximal significant increase in trend at p < 0.05 for BW gained with the percentage BW gain recording 62.98% and 63.55% respectively, but lower when compared to control
Mean kidney weight corresponds with the percentage BW gained across groups with the control group having an optimal mean kidney weight (Table 1)

Summary

Introduction

The successful introduction of highly active antiretroviral therapy (HAART) for the management of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) significantly increased the life expectancy among HIV-infected patients with unprecedented changes in disease progression and mortality [1] Despite this full control, empirical evidence still demonstrates that nephrotoxicity is increasing rapidly among people living with HIV and AIDS (PLWHA) dampening the perceived impact of HAART. Toxicology Reports 5 (2018) 1153–1160 reverse transcriptase of HIV along with inhibition of mitochondrial deoxyribonucleic acid (DNA) polymerase from host cells with subsequent deficits in mitochondrial DNA encoded enzymes [2].

Objectives

Methods

Results

Conclusion